PREPARATION AND CHARACTERIZATION OF A CHIMERIC-CD19 MONOCLONAL-ANTIBODY

被引:75
作者
ZOLA, H [1 ]
MACARDLE, PJ [1 ]
BRADFORD, T [1 ]
WEEDON, H [1 ]
YASUI, H [1 ]
KUROSAWA, Y [1 ]
机构
[1] FUJITA HLTH UNIV,INST COMPREHENS MED SCI,TOYOAKE,AICHI,JAPAN
关键词
D O I
10.1038/icb.1991.58
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
FMC63 is an IgG2a mouse monoclonal antibody belonging to the CD19 cluster. CD19 antibodies react with a 95kDa protein expressed by cells of the B lymphocyte lineage, from pre-B cells to mature B lymphocytes. CD19 antibodies have been suggested as candidates for immunological attack on leukaemic and lymphonia cells of the B lineage because the antigen is restricted to the B lineage. With the potential use of FMC63 in immunotherapy in mind, we have produced a mouse-human chimera in which the genes coding for the VDJ region of the heavy chain and the VJ region of the light chain derive from the FMC63 mouse hybridoma, while the C region genes code for human IgG1. The genes have been transfected back into a mouse myeloma line, which secretes low levels of immunoglobulin. (Ig). This Ig was purified and biotinylated in order to determine the specificity of the antibody. The chimeric antibody has a reaction profile concordant with the original FMC63 antibody, but has the properties of a human IgG1, including the ability to fix human complement. However, the antibody is not cytotoxic in virto in the presence of complement or cells capable of mediating antibody-dependent cellular cytotoxicity. Possible reasons for this and ways of using the antibody are discussed.
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页码:411 / 422
页数:12
相关论文
共 47 条
[1]  
BACH JF, 1972, BEHRING I MITT, P23
[2]  
BALNER H, 1972, BEHRING I MITT, V51, P1
[3]  
BERNSTEIN ID, 1980, MONOCLONAL ANTIBODIE, P275
[4]   HUMAN MONOCLONAL IGG ISOTYPES DIFFER IN COMPLEMENT ACTIVATING FUNCTION AT THE LEVEL OF C-4 AS WELL AS CLQ [J].
BINDON, CI ;
HALE, G ;
BRUGGEMANN, M ;
WALDMANN, H .
JOURNAL OF EXPERIMENTAL MEDICINE, 1988, 168 (01) :127-142
[5]   PRODUCTION OF FUNCTIONAL CHIMAERIC MOUSE HUMAN-ANTIBODY [J].
BOULIANNE, GL ;
HOZUMI, N ;
SHULMAN, MJ .
NATURE, 1984, 312 (5995) :643-646
[6]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[7]   COMPARISON OF THE EFFECTOR FUNCTIONS OF HUMAN-IMMUNOGLOBULINS USING A MATCHED SET OF CHIMERIC ANTIBODIES [J].
BRUGGEMANN, M ;
WILLIAMS, GT ;
BINDON, CI ;
CLARK, MR ;
WALKER, MR ;
JEFFERIS, R ;
WALDMANN, H ;
NEUBERGER, MS .
JOURNAL OF EXPERIMENTAL MEDICINE, 1987, 166 (05) :1351-1361
[8]   THE IMMUNOGENICITY OF CHIMERIC ANTIBODIES [J].
BRUGGEMANN, M ;
WINTER, G ;
WALDMANN, H ;
NEUBERGER, MS .
JOURNAL OF EXPERIMENTAL MEDICINE, 1989, 170 (06) :2153-2157
[9]   ISOLATION OF BIOLOGICALLY-ACTIVE RIBONUCLEIC-ACID FROM SOURCES ENRICHED IN RIBONUCLEASE [J].
CHIRGWIN, JM ;
PRZYBYLA, AE ;
MACDONALD, RJ ;
RUTTER, WJ .
BIOCHEMISTRY, 1979, 18 (24) :5294-5299
[10]  
COLCHER D, 1989, CANCER RES, V49, P1738